Retinal eye diseases are the leading cause of blindness in the Western world. Up to date, the only efficient treatment for many retinal diseases consists of invasive intravitreal injections of highly concentrated drugs. Despite the fact that these injections are unpleasant for the patients, they potentially cause serious side effects, e.g., infections, bleeding within the eye or retinal detachment, especially when performed on a monthly basis, thus decreasing the injection frequency and lowering the desired drug dose. Therefore, a sustained released at the region of interest with a sustained release is desired. Recently, novel lipid-DNA nanoparticles (NPs) were shown to be an efficient drug delivery platform to the anterior segment of the eye. In this study, we investigated the distribution and tropism of the NPs when applied intravitreally, as a potential medication carrier to the posterior part of the eye. This technology is perfectly suited for the delivery of low molecular weight drugs to the back of the eye, which so far is greatly hindered by fast diffusion rates of the free drugs in the vitreous body and their intrinsically low retainability in ocular tissue. Excellent biodistribution, adherence and presence for up to five days was found for the different tested nanoparticles ex vivo and in vivo. In conclusion, our lipid-DNA based nanocarrier system was able to reach the retina within minutes and penetrate the retina providing potentially safe and long-term carrier systems for small molecules or nucleotide-based therapies.
机构:
Univ Oklahoma, Hlth Sci Ctr, Dept Ophthalmol, Oklahoma City, OK 73104 USA
Dean McGee Eye Inst, Oklahoma City, OK 73104 USAUniv Oklahoma, Hlth Sci Ctr, Dept Ophthalmol, Oklahoma City, OK 73104 USA
Wang, Yuhong
Rajala, Ammaji
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Univ Oklahoma, Hlth Sci Ctr, Dept Ophthalmol, Oklahoma City, OK 73104 USA
Dean McGee Eye Inst, Oklahoma City, OK 73104 USAUniv Oklahoma, Hlth Sci Ctr, Dept Ophthalmol, Oklahoma City, OK 73104 USA
Rajala, Ammaji
Rajala, Raju V. S.
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Univ Oklahoma, Hlth Sci Ctr, Dept Ophthalmol, Oklahoma City, OK 73104 USA
Dean McGee Eye Inst, Oklahoma City, OK 73104 USA
Univ Oklahoma, Hlth Sci Ctr, Dept Physiol, Oklahoma City, OK 73104 USA
Univ Oklahoma, Hlth Sci Ctr, Dept Cell Biol, Oklahoma City, OK 73104 USAUniv Oklahoma, Hlth Sci Ctr, Dept Ophthalmol, Oklahoma City, OK 73104 USA
机构:
EyePoint Pharmaceut, Watertown, MA USA
Tufts Univ, New England Eye Ctr, Boston, MA USARetina Consultants Texas, 4460 Bissonnet St,Ste 200, Bellaire, TX 77401 USA
Duker, Jay S.
Altaf, Syed
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EyePoint Pharmaceut, Watertown, MA USARetina Consultants Texas, 4460 Bissonnet St,Ste 200, Bellaire, TX 77401 USA
Altaf, Syed
Saim, Said
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EyePoint Pharmaceut, Watertown, MA USARetina Consultants Texas, 4460 Bissonnet St,Ste 200, Bellaire, TX 77401 USA